Kowalczyk Malgorzata, Owczarek Aleksander J, Kucia Krzysztof, Hasterok Maja, Suchanek-Raif Renata, Paul-Samojedny Monika, Lakomy Weronika, Kowalski Jan
Department of Medical Genetics, Faculty of Pharmaceutical Sciences, Medical University of Silesia, Jedności 8, 41-200 Sosnowiec, Poland.
Health Promotion and Obesity Management Unit, Department of Pathophysiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medyków 15, 40-752 Katowice, Poland.
Genes (Basel). 2025 Sep 16;16(9):1092. doi: 10.3390/genes16091092.
Schizophrenia (SCZ) is a highly heritable mental disorder with a complex polygenic genetic architecture. The heat shock protein 90 alpha (HSP90α), encoded by the gene, is a molecular chaperone that is required for the proper folding and activity of many of the client proteins that are involved in numerous essential cellular pathways. In addition to its general chaperone activity, HSP90α plays a role in other neuronal contexts and was found to have an altered expression in SCZ, which makes an attractive gene for association studies. The aim of this study was to determine whether the polymorphisms (rs8005905, rs10873531, rs11621560, rs4947 and rs2298877) are involved in the risk of developing SCZ and its clinical picture in a Polish Caucasian population. : A total of 1088 unrelated subjects (409 patients and 679 healthy controls) were included in the study. The SNPs were genotyped using a TaqMan 5'-exonuclease allelic discrimination assay. The results of the Positive and Negative Syndrome Scale (PANSS) were presented in the five-dimensional model. : None of the SNPs were associated with a predisposition to developing SCZ in either the single-marker or haplotype analysis including the results of gender-stratified analyses. However, the genotypes of rs11621560, rs4947 and rs2298877 SNPs were associated with the emotional distress (EMO) dimension score. : The results of the present study indicate that variants may have an impact on the psychopathology of SCZ, although larger studies are needed to clarify these findings.
精神分裂症(SCZ)是一种具有高度遗传性的精神障碍,其遗传结构复杂且呈多基因特征。由该基因编码的热休克蛋白90α(HSP90α)是一种分子伴侣,许多参与众多重要细胞通路的客户蛋白的正确折叠和活性都需要它。除了其一般的伴侣活性外,HSP90α在其他神经元环境中也发挥作用,并且发现在SCZ中其表达发生了改变,这使得它成为关联研究中一个有吸引力的基因。本研究的目的是确定这些多态性(rs8005905、rs10873531、rs11621560、rs4947和rs2298877)是否与波兰白种人群中患SCZ的风险及其临床表现有关。方法:本研究共纳入1088名无亲属关系的受试者(409例患者和679名健康对照)。使用TaqMan 5'-外切核酸酶等位基因鉴别分析对单核苷酸多态性(SNP)进行基因分型。阳性和阴性症状量表(PANSS)的结果以五维模型呈现。结果:在单标记或单倍型分析中,包括性别分层分析的结果,没有一个SNP与患SCZ的易感性相关。然而,rs11621560、rs4947和rs2298877 SNP的基因型与情绪困扰(EMO)维度得分相关。结论:本研究结果表明,这些变体可能对SCZ的精神病理学有影响,尽管需要更大规模的研究来阐明这些发现。